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Background & Aims: Outcomes of endoscopic surveillance after surgery for colorectal cancer (CRC) vary with the incidence and timing of CRC detection at anastomoses or non-anastomoses in the colorectum. We performed a systematic review and meta-analysis to evaluate the incidence of CRCs identified during surveillance colonoscopies of patients who have already undergone surgery for this cancer., Methods: We searched PubMed, EMBASE, SCOPUS, and the Cochrane Central Register of Clinical Trials through January 1, 2018 to identify studies investigating rates of CRCs at anastomoses or other locations in the colorectum after curative surgery for primary CRC. We collected data from published randomized controlled, prospective, and retrospective cohort studies. Data were analyzed by multivariate meta-analytic models., Results: From 2373 citations, we selected 27 studies with data on 15,803 index CRCs for analysis (89% of patients with stage I-III CRC). Overall, 296 CRCs at non-anastomotic locations were reported over time periods of more than 16 years (cumulative incidence, 2.2% of CRCs; 95% confidence interval [CI], 1.8%-2.9%). The risk of CRC at a non-anastomotic location was significantly reduced more than 36 months after resection compared with before this time point (odds ratio for non-anastomotic CRCs at 36-48 months vs 6-12 months after surgery, 0.61; 95% CI, 0.37-0.98; P = .031); 53.7% of all non-anastomotic CRCs were detected within 36 months of surgery. One hundred and fifty-eight CRCs were detected at anastomoses (cumulative incidence of 2.7%; 95% CI, 1.9%-3.9%). The risk of CRCs at anastomoses was significantly lower 24 months after resection than before (odds ratio for CRCs at anastomoses at 25-36 months after surgery vs 6-12 months, 0.56; 95% CI, 0.32-0.98; P = .036); 90.8% of all CRCs at anastomoses were detected within 36 months of surgery., Conclusions: After surgery for CRC, the highest risk of CRCs at anastomoses and at other locations in the colorectum is highest during 36 months after surgery-risk decreases thereafter. Patients who have undergone CRC resection should be evaluated by colonoscopy more closely during this time period. Longer intervals may be considered thereafter., (Copyright © 2019 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Population-based endoscopic studies are needed to assess the epidemiology of functional dyspepsia (FD) and the newly suggested subgroups of meal-related symptoms and epigastric pain. We evaluated the prevalence of, and risk factors for, FD in the Italian general population., Methods: A total of 1533 inhabitants of 2 villages were invited to undergo symptom evaluation using a validated questionnaire, esophagogastroduodenoscopy, and (13)C-urea breath test; 1033 subjects (67.4%) took part., Results: Of the 1033 subjects, 156 (15.1%; 95% confidence interval [CI], 12.9-17.3) had dyspepsia, and of these 114 (11%; 95% CI, 9.2-12.9) had FD. Of the 114 subjects with FD, 77 (67.5%) had meal-related symptoms (postprandial fullness and/or early satiation) and 55 (48.2%) had epigastric pain. Only 18 subjects (15.8%) had both meal-related symptoms and epigastric pain; this was fewer than expected by chance alone (P < .001). Unemployment (odds ratio [OR], 5.80; 95% CI, 1.56-21.60), divorce (OR, 2.76; 95% CI, 1.10-6.91), smoking (OR, 1.74; 95% CI, 1.11-2.70), and irritable bowel syndrome (OR, 3.38; 95% CI, 1.85-6.19) were significantly associated with FD. Unemployment, divorce, and irritable bowel syndrome were associated with both meal-related symptoms and epigastric pain, while smoking was associated only with meal-related symptoms., Conclusions: FD is present in 11% of the Italian general population. Unemployment and divorce seem to increase the risk of FD, and smoking seems to be associated with meal-related symptoms. Two distinct subgroups of FD, as suggested by Rome III, seem to exist in the general population., (2010 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Increasing evidence indicates that inherited susceptibility is important in the pathogenesis of colorectal neoplasia. The aim of this study was to clarify whether having only one first-degree relative with colorectal cancer increases the risk of developing adenomatous polyps and whether total colonoscopy is an appropriate screening measure in these patients., Methods: The frequency of such a history was evaluated in 397 asymptomatic patients who underwent total colonoscopy. Of these patients, 155 had colorectal polyps and the remaining 242 did not have polyps., Results: Among polyp cases, 27 of 155 (17.4%) had a positive history; among those without polyps, 12 of 242 (5.0%) had a positive history. Alternatively expressed, 27 of 39 patients (69%) with family history and 128 of 358 patients (36%) without family history had adenomas. The estimated risk for polyps associated with family history was 1.9. Among polyp cases, 14 of 27 patients (51.9%) with family history and 32 of 128 patients (25.0%) without family history had only proximal polyps (chi 2 test; P = 0.006; odds ratio, 3.2), In the same groups, frequency of high-grade dysplasia was 8 of 27 patients (29.6%) and 16 of 128 patients (12.5%), respectively (chi 2 test; P = 0.04; odds ratio, 2.9)., Conclusions: Relative to subjects with no family history, asymptomatic patients with one first-degree relative with colorectal cancer had nearly double the risk of developing adenomatous polyps, greater frequency of severely dysplastic lesions, and significantly higher frequency of proximal polyp location. This suggests that total colonoscopy screening is indicated in these subjects.

Obesity is a condition associated with an increased frequency of gallstone disease. This study attempted to evaluate the comparative effects of two gallstone-dissolving agents, chenodeoxycholic acid and ursodeoxycholic acid, on bile acid metabolism and biliary lipid secretion in obese subjects in order to identify the bile acid of choice in preventing and treating gallstone disease in obesity. Twenty obese subjects (greater than 120% ideal body wt) were randomly treated with ursodeoxycholic acid (10 mg.kg-1.day-1.1 mo-1) and then with chenodeoxycholic acid (15 mg.kg-1.day-1.1 mo-1) or with chenodeoxycholic acid first and then with ursodeoxycholic acid. Patients 1-10 were studied while eating an unrestricted weight-maintenance diet, whereas patients 11-20 were eating a 1080-kcal/d hypocaloric diet. Biliary lipid composition, cholesterol saturation index, and biliary bile acid pattern were evaluated in all subjects before and after each treatment period; in subjects 6-10 and 16-20, biliary lipid secretion rates and bile acid pool size were also evaluated. Both ursodeoxycholic acid and chenodeoxycholic acid decreased cholesterol outputs and cholesterol saturation index. However, during the weight-maintenance period the decrease induced by chenodeoxycholic acid was not significant. Biliary cholesterol outputs and cholesterol saturation index were always lower during ursodeoxycholic acid administration than during chenodeoxycholic acid therapy. Ursodeoxycholic acid levels during ursodeoxycholic acid administration and chenodeoxycholic acid levels during chenodeoxycholic acid administration increased in bile to 50% and 77%, respectively, of total bile acid levels. Bile acid pool size remained unchanged during chenodeoxycholic acid administration and was significantly reduced by ursodeoxycholic acid administration during the weight-reduction period. In conclusion, ursodeoxycholic acid in obese subjects seems more effective than chenodeoxycholic acid, at least during weight maintenance, in reducing cholesterol saturation of bile. This effect is related to a significant decrease of biliary cholesterol output.

Gallbladder motility was evaluated by ultrasonography in 75 cholesterol gallstone patients and in 77 matched control subjects. All 75 gallstone patients were candidates for oral bile acid therapy (radiolucent gallstones, less than 2 cm in diameter, in well-opacified gallbladder), and 38 of them were also studied during ursodeoxycholic acid administration. An additional 20 gallstone patients were studied 1 year after confirmed gallstone dissolution with oral bile acids. Gallstone patients showed significantly greater fasting and residual volumes, a decreased percent of gallbladder emptying, but a similar absolute emptying and emptying rate compared with the control subjects. Greater fasting volumes and reduced percents of gallbladder emptying were also found in gallstone-free patients who achieved complete dissolution with oral bile acids. After ursodeoxycholic acid administration, fasting gallbladder volumes were greater, and percents of gallbladder emptying were further decreased than in untreated gallstone patients. In conclusion, greater fasting volumes, and not reduced gallbladder contractility, account for the defective gallbladder function in radiolucent (cholesterol-rich) gallstone patients. This condition is likely to precede, and possibly to promote, gallstone formation because it persists after gallstone dissolution. Ursodeoxycholic acid administration worsens the defect observed in gallstone patients. This finding also suggests, although indirectly, that the expected normalization of cholesterol saturation during oral bile acid administration is not paralleled by an improvement in gallbladder function.

The rate of decrease of gallstone diameter appeared to be linear with oral bile acid treatment time, as estimated by inspection of graphic data of individual patient serial oral cholecystograms. A theoretical basis for this model was derived. The hypothesis of diameter decrease proportional to treatment time was tested with data from 223 patients with radiolucent gallbladder stones up to 20 mm in diameter treated with 7-8 or 14-15 mg.kg-1.day-1 of either ursodiol or chenodiol for 1 year, followed up after 3, 6, and 12 months of treatment. Linearity of individual sets of data points was tested by mathematical and statistical methods, including polynomial curve fitting, linear regression analysis, quadratic vs. linear analyses of covariance, and prediction of 12-month stone size by linear extrapolation from diameters at 0 and 6 months. Most patients (greater than 70%) had rates of gallstone diameter decrease that were almost linear with treatment time, independently of different dissolution rates on a given regimen. Additional treatment time needed may be estimated from cholecystograms or ultrasonograms performed before treatment and after several months.

The comparative rate of formation of lithocholic acid from chenodeoxycholic acid and its 7 beta epimer, ursodeoxycholic acid, was studied in human subjects and in a rhesus monkey. [24-14C]Chenodeoxycholic acid and [24-14C]ursodeoxycholic acid were incubated in vitro, under anaerobic conditions, in fecal samples from 7 control and 7 asymptomatic gallstone subjects. The incubations were carried out for 0, 0.5, 1, 4, and 12 h. In addition, the labeled precursors were instilled into the colon of 4 asymptomatic gallstone patients and a rhesus monkey in which a bile duct fistula had been created. Radioactive metabolites were analyzed by thin-layer chromatography in the in vitro fecal incubates and in the in vivo colonic aspirates, stool, and bile. The biotransformation of the unlabeled material was analyzed by gas-liquid chromatography in the in vitro incubates and in the in vivo fecal samples of the rhesus monkey. There was no statistical difference between chenodeoxycholic and ursodeoxycholic acids in their rate of biotransformation to lithocholic acid, when the total group of 14 subjects was compared. However, among these 14, a subgroup of 4 subjects (2 controls and 2 with gallstones) was identified in whom the rate of degradation to lithocholic acid was significantly faster for chenodeoxycholic than for ursodeoxycholic acid. Increases in the concentrations of the precursors led to a decrease in the rate, but not a change in the comparative pattern of lithocholic acid formation. At the lower concentrations, the conversion of both bile acids to lithocholic acid was almost complete after 12 h. In the in vivo studies, the formation of lithocholic acid from chenodeoxycholic and ursodeoxycholic acids was comparable both in the 4 human subjects and in the rhesus monkey. The results of this study indicate that, in most cases, the risk of liver damage from lithocholic acid formation should be similar for both epimers. However, there appears to be a small population in which this risk could be higher during chenodeoxycholic acid than during ursodeoxycholic acid treatment due to a more rapid formation of lithocholic acid.

Recurrence is a major problem in the medical treatment of gallstones but its extent is still uncertain. The aim of this study was to determine the magnitude of this event and to assess the effectiveness of a postdissolution treatment in preventing it. We evaluated the long-term recurrence rate after 96 confirmed dissolutions observed in 86 subjects (71 women, 15 men) over a 12-yr follow-up period. A low-dose postdissolution treatment (ursodeoxycholic acid, 300 mg/day) was administered to 36 subjects, whereas in the remaining 60 cases no postdissolution treatment was given. By actuarial life-table analysis, the cumulative proportion of gallstone recurrence was 12.5% at the first year, rising to 61% at the 11th year. Postdissolution treatment was effective in reducing the frequency of gallstone recurrence (p = 0.0067), but this was mainly related to its effect on younger subjects (less than or equal to 50 yr old). In older subjects the recurrence rate was unaffected by treatment. The probability of gallstone recurrence was significantly higher in subjects with multiple stones before dissolution treatment than in those who had had solitary stones (p = 0.0091). No other factor predictive of gallstone recurrence could be identified.